Physiology Commons^™

The Microvascular And Systemic Effects Of Titanium Dioxide Nanoparticle Exposure: A Physiological Perspective, Alaeddin Bashir Abukabda

Graduate Theses, Dissertations, and Problem Reports (ETD)

Titanium dioxide nanoparticles (nano-TiO₂) are one of the most widely used engineered nanomaterials (ENM). Their ubiquitous inclusion warrants a more thorough understanding of their toxicity, particularly in sensitive populations such as pregnant women and the developing fetus.

The aim of the first study was to determine the most sensitive segments of the vasculature to pulmonary ENM exposure. Macrovascular function was investigated in the thoracic aorta, common femoral artery and 3^rd order mesenteric arterioles using wire myography. Microvascular function was assessed in 4^th and 5^th order mesenteric arterioles via pressure myography. Nano-TiO₂ exposure induced impairments …

Serine-Dependent Sphingolipid Synthesis Is A Metabolic Liability Of Aneuploid Cells, Sunyoung Hwang, H. Tobias Gustafsson, Ciara O’Sullivan, Gianna Bisceglia, Xinhe Huang, Christian Klose, Andrej Schevchenko, Robert C. Dickson, Paola Cavaliere, Noah Dephoure, Eduardo M. Torres

Molecular and Cellular Biochemistry Faculty Publications

Aneuploidy disrupts cellular homeostasis. However, the molecular mechanisms underlying the physiological responses and adaptation to aneuploidy are not well understood. Deciphering these mechanisms is important because aneuploidy is associated with diseases, including intellectual disability and cancer. Although tumors and mammalian aneuploid cells, including several cancer cell lines, show altered levels of sphingolipids, the role of sphingolipids in aneuploidy remains unknown. Here, we show that ceramides and long-chain bases, sphingolipid molecules that slow proliferation and promote survival, are increased by aneuploidy. Sphingolipid levels are tightly linked to serine synthesis, and inhibiting either serine or sphingolipid synthesis can specifically impair the fitness …

Acute Resistance Exercise Induces Sestrin2 Phosphorylation And P62 Dephosphorylation In Human Skeletal Muscle, Nina Zeng, Randall F. D'Souza, Vandre C. Figueiredo, James F. Markworth, Llion A. Roberts, Jonathan M. Peake, Cameron J. Mitchell, David Cameron-Smith

Center for Muscle Biology Faculty Publications

Sestrins (1, 2, 3) are a family of stress-inducible proteins capable of attenuating oxidative stress, regulating metabolism, and stimulating autophagy. Sequestosome1 (p62) is also a stress-inducible multifunctional protein acting as a signaling hub for oxidative stress and selective autophagy. It is unclear whether Sestrin and p62^Ser403 are regulated acutely or chronically by resistance exercise (RE) or training (RT) in human skeletal muscle. Therefore, the acute and chronic effects of RE on Sestrin and p62 in human skeletal muscle were examined through two studies. In Study 1, nine active men (22.1 ± 2.2 years) performed a bout of single-leg strength …

Macrophage Migration Inhibitory Factor Mediates Protease-Activated Receptor 4-Induced Bladder Pain Through Urothelial High Mobility Group Box 1, Fei Ma, Dimitrios E. Kouzoukas, Katherine L. Meyer-Siegler, David E. Hunt, Lin Leng, Richard Bucala, Pedro L. Vera

Physiology Faculty Publications

Macrophage migration inhibitory factor (MIF) mediates pain although the mechanisms are not well understood. Urothelial activation of protease activated receptor 4 (PAR4) results in urothelial MIF release, urothelial high mobility group box 1 (HMGB1) release and bladder pain in mice without bladder inflammation. All three effects are prevented by MIF inhibition while intravesical disulfide HMGB1 alone can induce bladder pain. This study utilizes genetic MIF deletion to determine whether MIF mediates PAR4-induced bladder pain and is upstream of HMGB1-induced bladder pain. Wild type (C57/BL6) and MIF knockout (KO) mice were treated with intravesical PAR4 activating peptide or disulfide HMGB1 and …

Response Of Appetite And Appetite Regulating Hormones To Acute Hypoxia, Morgan Busboom, Robert Shute, Dustin Slivka

Journal of Human Performance in Extreme Environments

AIM: To determine the acute response of appetite and appetite regulating hormones after exposure to simulated altitude. METHODS: Seven males and five females (height: 178.9 ± 2.3 cm; weight: 77.3 ± 7.2 kg; body fat: 18.4 ± 1.7%) participated in two, three-hour trials in a hypoxic (5000 m) and normoxic (350 m) environment. Blood samples were collected prior to and immediately following three hours of exposure for the measurement of leptin, adiponectin, and acylated ghrelin. Appetite, acute mountain sickness, heart rate, blood oxygenation, tissue oxygenation, respiration rate, and whole body gases were also measured. RESULTS: Leptin was not different between …

The Vibe, Sarah P. Douglass

Capstones

The Vibe is a long-form narrative about where tech is taking the female orgasm. The piece concludes that physiological research is a required next step when creating the climax of the future.

http://sarahpdouglass.com

Organizational Effects Of Defeminizing Toxicants: Lessons Learned From An Environmental Sentinel Organism, The Fathead Minnow., Jonathan Ali

Theses & Dissertations

Endocrine disrupting compounds (EDCs) are chemicals that interfere with hormone function and are increasingly detected in aquatic environments, where they elicit adverse effects from exposed organisms. The toxicological effects of EDCs can be described as either activational (reversible) or organizational (irreversible), where the latter are associated with adverse outcomes in reproductive performance of adult fish. However, few studies have investigated the organizational impacts of anti-estrogenic or “defeminizing” EDCs, e.g. agrichemicals or pharmacological agents, in an environmentally-relevant or “sentinel” species. The objective of this study was to investigate the impacts of early-life EDC-initiated changes in estrogenic gene expression on organizational effects …

Cholesterol Regulation Of Pulmonary Endothelial Calcium Entry Following Chronic Hypoxia, Bojun Zhang

Biomedical Sciences ETDs

Chronic hypoxia (CH)-induced pulmonary hypertension (PH) is associated with diminished ATP-induced endothelial Ca2+ entry as well as membrane cholesterol in pulmonary arteries. Store-operated Ca2+ entry (SOCE) and depolarization-induced Ca2+ entry are major components of the response to ATP and are similarly decreased after CH. Because endothelium-dependent vasodilation is closely associated with pulmonary endothelial [Ca2+]i, the blunted agonist-induced Ca2+ influx in pulmonary artery endothelial cells (PAEC) may contribute to the development of CH-induced PH. Interestingly, impaired agonist-induced Ca2+ influx in PAEC following CH can be restored by membrane cholesterol supplementation. In the current studies, we hypothesized that impaired Ca2+ entry in …

Methylglyoxal Requires Ac1 And Trpa1 To Produce Pain And Spinal Neuron Activation, Ryan B. Griggs, Don E. Laird, Renee R. Donahue, Weisi Fu, Bradley K. Taylor

Physiology Faculty Publications

Methylglyoxal (MG) is a metabolite of glucose that may contribute to peripheral neuropathy and pain in diabetic patients. MG increases intracellular calcium in sensory neurons and produces behavioral nociception via the cation channel transient receptor potential ankyrin 1 (TRPA1). However, rigorous characterization of an animal model of methylglyoxal-evoked pain is needed, including testing whether methylglyoxal promotes negative pain affect. Furthermore, it remains unknown whether methylglyoxal is sufficient to activate neurons in the spinal cord dorsal horn, whether this requires TRPA1, and if the calcium-sensitive adenylyl cyclase 1 isoform (AC1) contributes to MG-evoked pain. We administered intraplantar methylglyoxal and then evaluated …

Hyperhomocysteinemia-Induced Gene Expression Changes In The Cell Types Of The Brain, Erica M. Weekman, Abigail E. Woolums, Tiffany L. Sudduth, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

High plasma levels of homocysteine, termed hyperhomocysteinemia, are a risk factor for vascular cognitive impairment and dementia, which is the second leading cause of dementia. While hyperhomocysteinemia induces microhemorrhages and cognitive decline in mice, the specific effect of hyperhomocysteinemia on each cell type remains unknown. We took separate cultures of astrocytes, microglia, endothelial cells, and neuronal cells and treated each with moderate levels of homocysteine for 24, 48, 72, and 96 hr. We then determined the gene expression changes for cell-specific markers and neuroinflammatory markers including the matrix metalloproteinase 9 system. Astrocytes had decreased levels of several astrocytic end feet …

Translating Genetic And Preclinical Findings Into Autism Therapies, Maria Chahrour, Robin Kleiman, M Chiara Manzini

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and repetitive/restrictive interests. ASD is associated with multiple comorbidities, including intellectual disability, anxiety, and epilepsy. Evidence that ASD is highly heritable has spurred major efforts to unravel its genetics, revealing possible contributions from hundreds of genes through rare and common variation and through copy-number changes. In this perspective, we provide an overview of the current state of ASD genetics and of how genetic research has spurred the development of in vivo and in vitro models using animals and patient cells to evaluate the impact of genetic mutations …

Resting Hormone Alterations And Injuries: Block Vs “Daily Undulating Periodization” Weight-Training Among Division I Track And Field Athletes, Keith B. Painter, Gregory N. Haff, Travis Triplett, Charles A. Stuart, Guy Hornsby, Michael W. Ramsey, Caleb D. Bazyler, Michael H. Stone

ETSU Faculty Works

No abstract provided.

Exercise, Cognition, And The Aging Process Among Active, Competitive, And Sedentary Middle-Aged And Older Adults, Katherine Adams

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose This study aimed to compare the cognitive measures of reaction time and dual-task performance among recreationally active, master athletes, and sedentary older adults aged 50 years or older. Methods 59 late middle-aged and older adults between the ages of 50 to 88 years old participated in reaction time and dual-task tests of which consisted of multiple trials on the same day. Subjects were placed either into the recreationally active, masters athlete, or sedentary activity level group based on the Rapid Assessment of Physical Activity (RAPA) form. For the gait speed with associated dual-task component, subjects walked 10-meters at two …

Effects Of Temperature On Growth And Molting In Blue Crabs (Callinectes Sapidus) And Lesser Blue Crabs (Callinectes Similis), Abigail Ann Kuhn

Master's Theses

Temperature can exert impacts on many processes in ectotherms. With global temperatures rising due to climate change, many ectothermic species may exhibit changes in growth rates and size at maturity, and these changes can have population-level effects. Predicting responses of species to climate change will require not only knowledge of thermal tolerance limits, but also effects of temperature change on growth rates and other life history parameters. For arthropods that exhibit discontinuous growth (i.e., molting), this includes both intermolt period and growth per molt. Previous laboratory and field experiments suggest that temperature affects both intermolt period (IMP) and growth per …

Combined Effects Of Dissolved Oxygen And Temperature On Aerobic Respiration And Respiratory Recovery Responses Of The Spioniform Polychaete, Streblospio Gynobranchiata, In Relation To Body Size, Alyssa Bennett

Master's Theses

Elevated surface temperatures exacerbate the threat of hypoxia within coastal ecosystems. These two primary stressors likely interact as they elicit opposing physiological responses from marine organisms. Metabolic depression is typically associated with hypoxia, while metabolic rates increase with temperature. Moreover, physiological effects of combined stressors may not be additive. In light of increasing pressures from hypoxia, elevated ocean temperatures, and other stressors within coastal regions, studies need to examine effects of multiple stressors on physiology of coastal organisms.

Mass-specific aerobic respiration (V_O2) was characterized as a proxy for metabolic cost of Streblospio gynobranchiata, at combined levels of …

The Effects Of Continuous Insulin Pump Therapy On Glycemic Control In Pregnant Type 1 Diabetics, Kimberly Kelsey

Senior Theses

Type 1 Diabetics have various ways of managing their diabetes that have been studied for their effectiveness. Pregnancy in the Type 1 Diabetic has been understudied. It is known that Diabetics in general have poorer pregnancy outcomes because of poor glycemic control. This coupled with the fact that the body needs 3-4 times more insulin as pregnancy comes to an end makes managing blood glucose levels challenging for diabetics (Lowdermilk, 2016, p. 689). For the Type 1 Diabetic, there are two main ways to control diabetes: multiple daily injections using at least two type of insulin and continuous subcutaneous insulin …

Validation Of The Short Recovery Stress Scale Questionnaire During Women’S Volleyball In-Season Training, Asher Flynn, Joseph Walters, Henry Lang, Alec Perkins, Jacob Goodin, Caleb D. Bazyler

ETSU Faculty Works

No abstract provided.

Sustained Sensitizing Effects Of Tumor Necrosis Factor Alpha On Sensory Nerves In Lung And Airways, Ruei-Lung Lin, Qihai Gu, Mehdi Khosravi, Lu-Yuan Lee

Physiology Faculty Publications

Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and …

Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Physiology Faculty Publications

The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP‐21. We previously demonstrated that TLQP‐21 elicits hyperalgesia and contributes to nerve injury‐induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP‐21. We propose a novel neuroimmune signaling pathway involving TLQP‐21‐induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual‐ligand activation of C3aR1 by a neuropeptide (TLQP‐21) and an immune mediator (C3a) represents a …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations and Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …